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Sci Rep. 2015 Nov 25;5:16775. doi: 10.1038/srep16775.

The prognostic values of CYP2B6 genetic polymorphisms and metastatic sites for advanced breast cancer patients treated with docetaxel and thiotepa.

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Beijing Key Laboratory of Therapeutic Cancer Vaccines, Beijing Shijitan Hospital, Capital Medical University Cancer Center, 10 Tieyi Road, Beijing 100038, China.
Department of Medical Oncology, Peking University Cancer Hospital &Institute. 52 Fucheng Rd, Beijing 100142, China.
Department of Digestive Diseases, Beijing Friendship Hospital, Capital Medical University, Yongan Road 95, Beijing 100050, China.
Department of Surgery, Duke University Medical Center, 203 Research Drive, Suite 433, Box 2606, Durham, NC 27710, United States.


This study investigated interactive effects of CYP2B6 genotypes and liver metastasis on the prognosis of metastatic breast cancer patients who received combined chemotherapy of docetaxel and thiotepa. Totally 153 patients were retrospectively genotyped rs8192719 (c.1294 + 53C > T) and rs2279343 (c.785A > G). Kaplan-Meier method and Cox Proportional Hazard Regression model were used to estimate the survival. Patients with liver metastasis had worsen prognosis, conferring a 2.26-fold high risk of progression and 1.93-fold high risk of death (p < 0.05). Both CT/TT genotype of rs8192719 (c.1294 +  3C > T) and AG genotype of rs2279343 (c.785A > G) prolonged survival (p < 0.05). Furthermore, among liver metastatic patients, AG genotype of rs2279343 (c.785A > G) was associated with a 47% reduced risk of death and a 6-month-longer overall survival (p < 0.05). Among non-liver metastatic patients, hazard ratios of CT/TT genotype of rs8192719 (c.1294 + 53C > T) were 0.45 for progression and 0.40 for death; and the corresponding survival was improved by 6 months and 16 months, respectively (p < 0.05). Genotypes of CYP2B6 had an interaction with clinical efficacy of docetaxel and thiotepa on metastatic breast cancer patients; and metastatic sites also affected clinical responses. Further therapies should take into account of chemotherapy regimen, genotypes of metabolizing enzymes and metastatic sites for the particular subpopulation.

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